The gating mechanism in cyclic nucleotide-gated ion channels

Cyclic nucleotide-gated (CNG) channels mediate transduction in several sensory neurons. These channels use the free energy of CNs’ binding to open the pore, a process referred to as gating. CNG channels belong to the superfamily of voltage-gated channels, where the motion of the α-helix S6 controls...

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Bibliographic Details
Published in:Scientific reports 2018-01, Vol.8 (1), p.45-15, Article 45
Main Authors: Mazzolini, Monica, Arcangeletti, Manuel, Marchesi, Arin, Napolitano, Luisa M. R., Grosa, Debora, Maity, Sourav, Anselmi, Claudio, Torre, Vincent
Format: Article
Language:English
Subjects:
631/57
631/61
Amino Acid Motifs
Binding Sites
Biochemistry
Biochemistry, Molecular Biology
Biophysics
Central nervous system
Channel gating
Channel opening
Chemical modification
Cyclic GMP
Cyclic Nucleotide-Gated Cation Channels - chemistry
Cyclic Nucleotide-Gated Cation Channels - genetics
Cyclic Nucleotide-Gated Cation Channels - metabolism
Electrophysiology
Free energy
Humanities and Social Sciences
Ion Channel Gating
Ion channels (cyclic nucleotide-gated)
Ions
Life Sciences
Models, Molecular
multidisciplinary
Mutation
Pharmaceutical sciences
Pharmacology
Position-Specific Scoring Matrices
Protein Binding
Protein Conformation
Protein Folding
Science
Science (multidisciplinary)
Sensory neurons
Site-directed mutagenesis
Spectroscopy
Structure-Activity Relationship
Voltage
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Summary:Cyclic nucleotide-gated (CNG) channels mediate transduction in several sensory neurons. These channels use the free energy of CNs’ binding to open the pore, a process referred to as gating. CNG channels belong to the superfamily of voltage-gated channels, where the motion of the α-helix S6 controls gating in most of its members. To date, only the open, cGMP-bound, structure of a CNG channel has been determined at atomic resolution, which is inadequate to determine the molecular events underlying gating. By using electrophysiology, site-directed mutagenesis, chemical modification, and Single Molecule Force Spectroscopy, we demonstrate that opening of CNGA1 channels is initiated by the formation of salt bridges between residues in the C-linker and S5 helix. These events trigger conformational changes of the α-helix S5, transmitted to the P-helix and leading to channel opening. Therefore, the superfamily of voltage-gated channels shares a similar molecular architecture but has evolved divergent gating mechanisms.
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-017-18499-0